Combination sustained release-immediate release oral dosage forms with an opioid analgesic and a non-opioid analgesic

• US 20030092724A1
• Filed: 09/17/2002
• Published: 05/15/2003
• Est. Priority Date: 09/18/2001
• Status: Abandoned Application

• Current Assignee: Endo Pharmaceuticals Incorporated (Endo International PLC)
• Original Assignee: Endo Pharmaceuticals Incorporated (Endo International PLC)
• Inventors: Kao, Huaihung, Zeng, Yadi, Jim, Fai
• Application Number:
  US10/245,139
• Publication Number:
  US 20030092724A1
• Time in Patent Office: Days
• US Class Current: 514/282
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer

Abstract

The present invention relates to new and useful oral tablet compositions which include an immediate release portion having an opioid analgesic and a non-opioid analgesic, providing for a rapid onset of therapeutic effect, and a sustained release portion of an opioid analgesic and a non-opioid analgesic, providing for a relatively longer duration of therapeutic effect. A multilayer oral dosage form containing a sustained release layer, which includes oxycodone and APAP, hydrocodone and APAP, or oxymorphone and APAP, and an immediate release layer containing the same active ingredients as the sustained release layer, is also disclosed. Also disclosed are oral tablet compositions, containing a sustained release core, which includes oxycodone and APAP, hydrocodone and APAP, or oxymorphone and APAP, and an immediate release coating containing the same active ingredients as the sustained release core, are also disclosed. In addition, methods of making and using such oral tablet compositions are disclosed.

Claims

1. A multilayer dosage form for oral administration comprising:

at least one layer comprising an opioid analgesic, a non-opioid analgesic, and a sustained release mechanism; and

at least another layer comprising an opioid analgesic and a non-opioid analgesic.

2. The dosage form of claim 1, wherein the dissolution profile for each of the opioid analgesic and non-opioid analgesic is between about 30% and about 65% released in about 1 hour and between about 55% and about 85% released in about 4 hours.

3. The dosage form of claim 2, wherein said dosage form is suitable for twice a day or three times a day administration.

4. The dosage form of claim 1, wherein the dissolution profile for each of the opioid analgesic and non-opioid analgesic is between about 15% and about 45% released in about 1 hour and between about 35% and about 65% released in about 4 hours.

5. The dosage form of claim 4, wherein said dosage from is suitable for once a day administration.

6. The dosage form of any of claims 1-3, wherein the at least one layer comprises oxycodone, APAP, and a sustained release mechanism, and the at least one additional layer comprises oxycodone and APAP.

7. The dosage form of any of claims 1-3, wherein the at least one layer comprises hydrocodone, APAP, and a sustained release mechanism, and the at least one additional layer comprises hydrocodone and APAP.

8. A dosage form of any of claims 1-3, wherein the at least one layer comprises oxymorphone, APAP, and a sustained release mechanism, and the at least one additional layer comprises oxymorphone and APAP.

9. The dosage form of claims 1, 4, or 5, wherein the at least one layer comprises oxycodone, APAP, and a sustained release mechanism, and the at least one additional layer comprises oxycodone and APAP.

10. The dosage form of claims 1, 4, or 5, wherein the at least one layer comprises hydrocodone, APAP, and a sustained release mechanism, and the at least one additional layer comprises hydrocodone and APAP.

11. A dosage form of claims 1, 4, or 5, wherein the at least one layer comprises oxymorphone, APAP, and a sustained release mechanism, and the at least one additional layer comprises oxymorphone and APAP.

29. A method of treating pain comprising administering the dosage form of any of claims 1-11 and 15-25 to a human or animal.

12. A method of making a multilayer oral dosage form comprising:

forming at least one layer comprising an opioid analgesic, a non-opioid analgesic, and a sustained release mechanism and compressing it; and

,

forming at least one additional layer comprising an opioid analgesic and a non-opioid analgesic and compressing it over the compressed first layer, or vice versa.

13. The method of claim 12, wherein the opioid analgesic is selected from the group consisting of oxycodone, hydrocodone and oxymorphone.

14. The method of claim 12 or 13, wherein the non-opioid analgesic is APAP.

15. A dosage form for oral administration comprising:

a sustained release core layer comprising an opioid analgesic, a non-opioid analgesic, and a sustained release mechanism; and

,

a coating layer comprising an opioid analgesic and a non-opioid analgesic.

16. The dosage form of claim 15, wherein the dissolution profile for each of the opioid analgesic and non-opioid analgesic is between about 30% and about 65% released in about 1 hour and between about 55% and about 85% released in about 4 hours.

17. The dosage form of claim 15, wherein said dosage form is suitable for twice a day or three times a day administration.

18. The dosage form of claim 15, wherein the dissolution profile for each of the opioid analgesic and non-opioid analgesic is between about 15% and about 45% released in about 1 hour and between about 35% and about 65% released in about 4 hours.

19. The dosage form of claim 18, wherein said dosage from is suitable for once a day administration.

20. The dosage form of any of claims 15-17, wherein the sustained release core comprises oxycodone, APAP, and a sustained release mechanism, and the IR coating layer comprises oxycodone and APAP.

21. The dosage form of any of claims 15-17, wherein the sustained release core comprises hydrocodone, APAP, and a sustained release mechanism, and the IR coating layer comprises hydrocodone and APAP.

22. The dosage form of any of claims 15-17, wherein the sustained release core comprises oxymorphone, APAP, and a sustained release mechanism, and the IR coating layer comprises oxymorphone and APAP.

23. The dosage form of claims 15, 18, or 19, wherein the sustained release core comprises oxycodone, APAP, and a sustained release mechanism, and the IR coating layer comprises oxycodone and APAP.

24. The dosage form of claims 15, 18, or 19, wherein the sustained release core comprises hydrocodone, APAP, and a sustained release mechanism, and the IR coating layer comprises hydrocodone and APAP.

25. The dosage form of claims 15, 18, or 19, wherein the sustained release core comprises oxymorphone, APAP, and a sustained release mechanism, and the IR coating layer comprises oxymorphone and APAP.

26. A method of making an oral dosage form comprising:

forming a core tablet comprising an opioid analgesic, a non-opioid analgesic, and a sustained release mechanism and compressing it; and

,

forming a coating over the core tablet comprising an opioid analgesic and a non opioid analgesic with an immediate release mechanism.

27. The method of claim 26, wherein the opioid analgesic is selected from the group consisting of oxycodone, hydromorphone and oxymorphone.

28. The method of claim 26 or 27, wherein the non-opioid analgesic comprises APAP.